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Perfluorinated hydrocarbons have been manufactured for over 40 years and have numerous applications in industry. This group of compounds has recently generated much interest as common metabolites (i.e., perfluorooctane sulfonate (PFOS); perfluoroctanic acid (PFOA)) are found to be persistent in the environment, have been detected in blood samples of both wildlife and humans, and appear to have a common mechanism of action. Studies show that these perfluorinated compounds cause peroxisomal proliferation, hepatomegaly, altered steroidogenesis, and body weight decreases that are associated with a wasting syndrome; however, effects on immune function have not been extensively assessed. This study examined the immunotoxicological effects of PFOS on the developing immune system should exposure occur during pregnancy. Therefore, C57BL/6N pregnant dams (mated with C3H/HeJ males) were orally exposed with 0, 0.1, 1.0 or 5.0 mg/kg of PFOS during each day of gestation. F1 offspring were evaluated for immunological alterations at 4 and 8 weeks of age. In general, there were no treatment effects on body, spleen, or thymus mass, and limited effects on kidney and liver mass. Corresponding flow cytometric analysis of CD4/CD8 lymphocytic subpopulations in the thymus and spleen were not altered in 4- or 8-week F1 mice. However, assessment of functional immunological parameters at 8-weeks of age revealed functional deficits. Natural killer cell activity was dose-responsively suppressed in both male and female F1 adults, whereas IgM plaque forming cell (PFC) responses were only suppressed in male F1 adults. Our data indicate that prenatal exposure to PFOS can suppress functional immunological responses that are evident at adulthood, with increased vulnerability exhibited in the male F1 offspring.